S1
Electronic Supplementary Information
CeCl3-mediated alkynylic 1,2-addition reaction of C-O acetylenic bis-lithium salts to
aldehydes and ketones. An efficient route to bis-substituted alkyne diols
Jefferson L. Princivala* and Jeiely G. Ferreiraa
Laboratório de Catálise Orgânica - Departamento de Química Fundamental-UFPE
Av. Jornalista Aníbal Fernandes s/n - Cidade Universitária - Recife-PE
CEP 50740-560 / Tel.:+55 (81) 2126-7463
Contents Page
Experimental S2
Data Analysis S3-S5
1H and 13C NMR spectra S6-S32
S2
Experimental
All solvents used in the reactions were purified by distillation prior to use. In the case of dry
THF (used to generate bis-lithium salts in the organometallic step), the solvent was dried at
reflux in the presence of pieces of metallic sodium using 1,10-phenantroline as an indicator.
The reactions were conducted in round bottom flasks fitted with rubber septa under a
positive nitrogen atmosphere flow and purified on flash silica 220-440 mesh particle size.
The reactions were monitored using aluminum TLC plates 20x20 cm on silica gel 60 of
Macherey-Nagel® and using a SHIMADZU
® 2010 Plus Gas chromatograph coupled with an
auto sampler for the flame ionization detector (FID) using N2 as the carrier gas.
The 1H at 300 MHz and
13C at 75 MHz NMR analysis were performed on a VARIAN
® Unity
Plus-300 (300 MHz) spectrometer, using deuterated chloroform (CDCl3) as solvent and Me4Si
as internal standard. The chemical shifts are expressed in ppm and coupling constants (J) are in
Hz.
General procedure for the preparation of diols 4-21
To a round bottom flask containing the propargylic alcohol (3 mmol) in THF (5 mL) at -40 0C under a dry N2 atmosphere with stirring, n-butyl lithium (6.6 mmol; 7.2 mL, 0.92 mol/L
solution in hexane) was added dropwise. After stirring the solution at the same temperature for
20 min, it was transferred to another round bottomed flask containing a previously prepared
mixture of the carbonyl compound (3mmol) and anhydrous CeCl3 (1.5 mmol) in THF (10 mL).
The reaction was monitored by TLC until consumption of the carbonyl compound, quenched
with a saturated solution of NH4Cl (2 mL) and the phases separated. The aqueous phase was
extracted with ethyl acetate (2 x 5 mL) washed with brine, dried with magnesium sulphate,
filtered, and the solvents removed using a rotary evaporator under vacuum. The crude was
purified by silica gel chromatography using n-hexane/ethyl acetate (1:1) as eluent.
S3
Pent-2-yne-1,4-diol (4) Colourless oil, yield (0.28g) 94%. 1HNMR (300 MHz;
CDCl3, ppm): δ 1.44 (3H, d, J = 6.3 Hz), 3.60 (2H, s), 4.28 (2H, d, J = 1.8 Hz), 4.57
(1H, qt, J = 6.3 Hz, J = 1.8 Hz); 13
CNMR(75 MHz; CDCl3, ppm): δ 24.0, 50.6, 58.1,
82.1, 87.5; CAS 927-57-1.
Hex-2-yne-1,4-diol (5) Colourless oil, yield (0.31g) 91%. 1HNMR (300 MHz;
CDCl3, ppm): δ 0.99 (3H, t, J = 7.5 Hz), 1.65-1.80 (2H, m), 3.99 (2H, s), 4.30
(2H, d, J = 1.5 Hz), 4.35 (1H, tt, J = 6.6 Hz, J = 1.5 Hz); 13
CNMR (75 MHz;
CDCl3, ppm): δ 9.4, 30.5, 50.4, 63.3, 82.9, 86.3; CAS 14092-35-4
Hept-3-yne-1,4-diol (6) Colourless oil, yield (0.38g) 100%. 1HNMR (300
MHz; CDCl3, ppm): δ 0.9 (3H, t, J = 7.5 Hz), 1.47 (2H, sext, J = 7.5 Hz), 1.60-
1.77 (2H, m), 3.58 (2H, s), 4.30 (2H, d, J = 1.8 Hz), 4.43 (1H, tt, J = 6.6 Hz, J
= 1.8 Hz); 13
CNMR (75 MHz; CDCl3, ppm): δ 13.6, 18.4, 39.5, 50.6, 61.9,
82.8, 86.6; CAS 18864-39-6
Non-2-yne-1,4-diol (7) Colourless oil, yield (0.47g) 100%. 1HNMR
(300 MHz; CDCl3, ppm): δ 0.90 (3H, t, J = 6.9 Hz), 1.25-1.50 (6H, m),
1.60-1.80 (2H, m), 3.31 (2H, s), 4.31 (2H, t, J = 1.8 Hz), 4.49 (1H, tt, J =
6.6 Hz, J = 1.8 Hz ); 13
CNMR (75 MHz; CDCl3, ppm): δ 13.9, 22.5,
24.8, 31.4, 37.4, 50.6, 62.2, 82.8, 86.7; CAS 98262-70-5
5-methylhex-2-yne-1,4-diol (8) Colourless oil, yield (0.38g) 100%. 1HNMR (300
MHz; CDCl3, ppm): δ 1.0 (6H, dd, J = 6 Hz), 1.88 (1H, oct, J = 6 Hz), 3.13 (2H,
s), 4.21 (1H, dt, J = 6 Hz, J = 1.5 Hz ), 4.32 (2H, d, J = 1.5 Hz); 13
CNMR (75
MHz; CDCl3, ppm): δ 17.5, 18.0, 34.3, 50.7, 67.7, 83.7, 85.3; CAS 35336-44-8
4-methylhex-2-yne-1,4-diol (9): Colourless oil, yield (0.35g) 90%. 1HNMR (300
MHz; CDCl3, ppm): δ 1.03 (3H, t, J = 7.5 Hz), 1.47 (3H, s), 1.71 (2H, q, J = 7.5
Hz), 2.88 (2H, s), 4.30 (2H, s); 13
CNMR (75 MHz; CDCl3, ppm): δ 8.93, 28.9,
36.2, 50.7, 68.6, 81.4, 89.1; CAS 920-09-2
S4
1-phenylbut-2-yne-1,4-diol (10) Solid, yield (0.49g) 100%.1HNMR (300
MHz; CDCl3, ppm): δ 2.22 (2H, s), 4.35 (2H, d, J = 1.8 Hz), 5.52 (1H, t, J =
1.8 Hz), 7.35-7.45 (3H, m), 7.5-7.6 (2H, m); 13
CNMR (75 MHz; CDCl3, ppm):
δ 51.0, 64.4, 84.8, 85.4, 126.5, 128.4, 128.6, 140.2; CAS 29021-82-7
1-(furan-2-yl)but-2-yne-1,4-diol (11) Colourless oil, yield (0.45g) 100%.
1HNMR (300 MHz; CDCl3, ppm): δ 4.35 (2H, d, J = 1.5 Hz), 5.51 (1H, t, J =
1.5 Hz), 6.35 (1H, dd, J = 3.3 Hz, J = 1.8 Hz ), 6.44 (1H, dt, J = 3.3 Hz, J = 0.9
Hz), 7.41 (1H, dd, J = 1.8 Hz, J = 0.9 Hz ); 13
CNMR (75 MHz; CDCl3, ppm): δ
50.4, 57.6, 82.7, 83.9, 107.7, 110.3, 142.9, 152.4; CAS 90111-26-5
1-(3-hydroxybut-1-yn-1-yl)cyclohexanol (12) Colourless oil, yield (0.45g)
90%. 1HNMR (300 MHz; CDCl3, ppm): δ 1.42 (3H, d, J = 6.6 Hz), 1.45-1.95
(10H, m), 3.67 (1H, s), 4.54 (1H, q, J = 6.6 Hz); 13
CNMR (75 MHz; CDCl3,
ppm): δ 23.2, 24.2, 25.1, 39.6, 57.9, 68.4, 86.1, 87.4; CAS 5111-47-7
1,1-diphenylpent-2-yne-1,4-diol (13) Colourless oil, yield (0.75g) 100%.
1HNMR (300 MHz; CDCl3, ppm): δ 1.51 (3H, d, J = 6.6 Hz), 4.64 (1H, q, J =
6.6 Hz), 7.2-7.4 (6H, m), 7.55-7.65 (4H, m); 13
CNMR (75 MHz; CDCl3, ppm):
δ 24.0, 58.3, 74.1, 86.6, 89.9, 125.9, 127.6, 128.2, 144.7; CAS 783339-46-8
(R,S)-2-metilhex-3-ino-2,5-diol. (14): Colourless oil, yield (0.35g) 91%.
1HNMR (300 MHz; CDCl3, ppm): δ 1.44 (3H, d, J = 6.6 Hz), 1.52 (6H, s), 3.13
(2H, s), 4.55 (1H, q, J = 6.6 Hz); 13
CNMR (75 MHz; CDCl3, ppm): δ 24.2, 31.2,
58.0, 64.9, 83.9, 88.6; CAS 5111-43-3
2-methyhept-3-yne-2,5-diol (15) Colourless oil, yield (0.39g) 93%. 1HNMR
(300 MHz; CDCl3, ppm): δ 0.96 (3H, t, J = 7.5 Hz), 1.49 (6H, s), 1.6-1.75 (2H,
m), 2.84 (2H, s), 4.30 (1H, t, J = 6.6 Hz); 13
CNMR (75 MHz; CDCl3, ppm): δ
9.4, 30.7, 31.3, 63.4, 65.0, 82.8, 89.5; CAS 41368-08-5
S5
2,6-dimethylhept-3-yne-2,5-diol (16) Colourless oil, yield (0.47g) 100%.
1HNMR (300 MHz; CDCl3, ppm): δ 0.98 (6H, dd, J = 6.6 Hz), 1.51 (6H, s),
1.85 (1H, oct, J = 6.6 Hz), 3.18 (2H, s), 4.16 (1H, d, J = 6.6 Hz; 13
CNMR (75
MHz; CDCl3, ppm): δ 17.4, 18.1, 31.2, 31.3, 34.3, 65.0, 67.5, 81.7, 90.2; CAS
5486-58-8
Hex-3-yne-1,5-diol (17) Colourless oil, yield (0.3g) 90%. 1HNMR (300 MHz;
CDCl3, ppm): δ 1.40 (3H, d, J = 6.6 Hz), 2.44 (2H, td, J = 6.6 Hz, J = 2.1 Hz),
2.73 (2H, s), 3.69 (2H, t, J = 6.3 Hz ), 4.49 (1H, qt, J = 6.3 Hz, J = 2.1 Hz);
13CNMR (75 MHz; CDCl3, ppm): δ 22.9, 24.4, 58.2, 60.8, 81.1, 84.1; CAS
488099-02-1
Hept-3-ine-1,5-diol (18) Colourless oil, yield (0.35g) 92%. 1HNMR (300
MHz; CDCl3, ppm): δ 1.0 (3H, d, J = 7.5 Hz), 1.6-1.8 (2H, m), 2.48 (2H, td, J
= 6 Hz, J = 2.1 Hz), 3.18 (2H, s), 3.72 (2H, t, J = 6 Hz), 4.31 (1H, tt, J = 6.6
Hz, J = 2.1 Hz); 13
CNMR (75 MHz; CDCl3, ppm): δ 9.4, 22.9, 30.9, 60.8,
63.6, 82.1, 82.9; CAS 1782972-32-0
6-methylhept-3-yne-1,5-diol (19) Colourless oil, yield (0.41g) 97%. 1HNMR
(300 MHz; CDCl3, ppm): δ 0.97 (6H, dd, J = 6.6 Hz), 1.83 (1H, oct, J = 6.6
Hz), 2.47 (2H, td, J = 6 Hz, J = 2.1 Hz), 2.87 (2H, s), 3.71 (2H, t, J = 6 Hz),
4.14 (1H, d, J = 6 Hz); 13
CNMR (75 MHz; CDCl3, ppm): δ 17.4, 18.1, 22.9,
34.5, 60.9, 67.9, 81.7, 82.7; CAS 20634-84-8
Hex-2-yne-1,5-diol (20) Colourless oil, yield (0.31g) 91%. 1HNMR (300 MHz;
CDCl3, ppm): δ 1.25 (3H, d, J = 6.3 Hz), 2.31 (1H, ddt, J = 16.3 Hz, J
= 6.6 Hz, J
= 2.1 Hz), 2.44 (1H, ddt, J = 16.3 Hz, J
= 6.6 Hz, J
= 2.1 Hz), 2.94 (2H, s), 3.97
(1H, sext, J = 6.6 Hz), 4.26 (2H, t, J
= 2.1 Hz);
13CNMR (75 MHz; CDCl3, ppm):
δ 22.2, 29.1, 51.0, 66.3, 80.7, 82.6; CAS 343268-16-6
S6
1HNMR (300 MHz, CDCl3) of 4.
S7
13CNMR (75 MHz, CDCl3) of 4.
1HNMR (300 MHz, CDCl3) of 5
S8
13CNMR (75 MHz, CDCl3) of 5
S9
1HNMR (300 MHz, CDCl3) of 6
S10
13CNMR (75 MHz, CDCl3) of 6
1HNMR (300 MHz, CDCl3) of 7
S11
13CNMR (75 MHz, CDCl3) of 7
S12
1HNMR (300 MHz, CDCl3) of 8
S13
13CNMR (75 MHz, CDCl3) of 8
S14
1HNMR (300 MHz, CDCl3) of 9
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13CNMR (75 MHz, CDCl3) of 9
1HNMR (300 MHz, CDCl3) of 10
S16
13CNMR (75 MHz, CDCl3) of 10
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1HNMR (300 MHz, CDCl3) of 11
S18
13CNMR (75 MHz, CDCl3) of 11
S19
1HNMR (300 MHz, CDCl3) of 12
S20
13CNMR (75 MHz, CDCl3) of 12
S21
1HNMR (300 MHz, CDCl3) of 13
S22
13CNMR (75 MHz, CDCl3) of 13
1HNMR (300 MHz, CDCl3) of 14
S23
13CNMR (75 MHz, CDCl3) of 14
S24
1HNMR (300 MHz, CDCl3) of 15
S25
13CNMR (75 MHz, CDCl3) of 15
1HNMR (300 MHz, CDCl3) of 16
S26
13CNMR (75 MHz, CDCl3) of 16
S27
1HNMR (300 MHz, CDCl3) of 17
13CNMR (75 MHz, CDCl3) of 17
S28
1HNMR (300 MHz, CDCl3) of 18
S29
13CNMR (75 MHz, CDCl3) of 18
S30
1HNMR (300 MHz, CDCl3) of 19
S31
13CNMR (75 MHz, CDCl3) of 19
1HNMR (300 MHz, CDCl3) of 20
S32
13CNMR (75 MHz, CDCl3) of 20